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Publication
A systematic review and meta-analysis of cell-based interventions in
experimental diabetic kidney disease.
Authors Hickson LJ, Abedalqader T, Ben-Bernard G, Mondy JM, Bian X, Conley SM, Zhu X,
Herrmann SM, Kukla A, Lorenz EC, Kim SR, Thorsteinsdottir B, Lerman LO, Murad MH
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Stem cells translational medicine
Year 2021
Date Published 9/1/2021
Volume : Pages 10 : 1304 - 1319
PubMed Reference 34106528
Abstract Regenerative, cell-based therapy is a promising treatment option for diabetic
kidney disease (DKD), which has no cure. To prepare for clinical translation,
this systematic review and meta-analysis summarized the effect of cell-based
interventions in DKD animal models and treatment-related factors modifying
outcomes. Electronic databases were searched for original investigations
applying cell-based therapy in diabetic animals with kidney endpoints (January
1998-May 2019). Weighted or standardized mean differences were estimated for
kidney outcomes and pooled using random-effects models. Subgroup analyses tested
treatment-related factor effects for outcomes (creatinine, urea, urine protein,
fibrosis, and inflammation). In 40 studies (992 diabetic rodents), therapy
included mesenchymal stem/stromal cells (MSC; 61%), umbilical cord/amniotic
fluid cells (UC/AF; 15%), non-MSC (15%), and cell-derived products (13%). Tissue
sources included bone marrow (BM; 65%), UC/AF (15%), adipose (9%), and others
(11%). Cell-based therapy significantly improved kidney function while reducing
injury markers (proteinuria, histology, fibrosis, inflammation, apoptosis,
epithelial-mesenchymal-transition, oxidative stress). Preconditioning,
xenotransplantation, and disease-source approaches were effective. MSC and UC/AF
cells had greater effect on kidney function while cell products improved
fibrosis. BM and UC/AF tissue sources more effectively improved kidney function
and proteinuria vs adipose or other tissues. Cell dose, frequency, and
administration route also imparted different benefits. In conclusion, cell-based
interventions in diabetic animals improved kidney function and reduced injury
with treatment-related factors modifying these effects. These findings may aid
in development of optimal repair strategies through selective use of
cells/products, tissue sources, and dose administrations to allow for successful
adaptation of this novel therapeutic in human DKD.




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